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Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

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Published on: October 9, 2016

MATR3 pathogenic variants differentially impair its cryptic splicing repression function.

Mashiat Khan^1,2, Xiao Xiao Lily Chen^1,2, Michelle Dias^3,4

¹Department of Molecular Genetics, University of Toronto, Canada.

|February 6, 2024

Summary

This summary is machine-generated.

Matrin-3 (MATR3) protein loss causes cryptic splicing errors in genes. Disease-linked MATR3 variants impair its function, impacting neurodegenerative and neurodevelopmental disease mechanisms.

Keywords:

MATR3 RNA-binding protein amyotrophic lateral sclerosis cryptic splicing neurodevelopmental disease

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Area of Science:

Molecular Biology
Genetics
Neuroscience

Background:

Matrin-3 (MATR3) is an RNA-binding protein associated with neurodegenerative and neurodevelopmental diseases.
The role of MATR3 in cryptic splicing within functional genes and the impact of disease variants remain largely unknown.

Purpose of the Study:

To investigate the function of MATR3 in regulating cryptic splicing in functional genes.
To determine how disease-associated MATR3 variants affect its RNA-binding, solubility, and splicing repression activities.

Main Methods:

Analysis of cryptic exon inclusion upon MATR3 loss.
Assessment of RNA binding and solubility for wild-type and variant MATR3 proteins.
Evaluation of the impact of variants on MATR3's cryptic splicing repression function.

Main Results:

Loss of MATR3 leads to widespread cryptic exon inclusion in various transcripts.
The ALS-linked S85C variant reduces MATR3 solubility but preserves RNA binding.
A novel neurodevelopmental disease variant, M548T, impairs MATR3 solubility, RNA binding, and cryptic splicing repression.

Conclusions:

MATR3 plays a critical role in repressing cryptic splicing events within functional genes.
Disease-associated MATR3 variants can disrupt its function through altered solubility and RNA binding, contributing to disease pathogenesis.